At the nonclinical experiment level, it is now becoming possible to treat disease-model animals using techniques of introducing genes of interest, or conversely, suppressing the expression of genes of interest through RNA interference. In the case of “nucleic acid pharmaceutical agents” using such a gene or an siRNA (generally termed “nucleic acid”), the nucleic acid administered to the living body needs to continuously produce its effect and be retained over a long period. A critical factor in achieving the therapeutic effect of nucleic acid pharmaceutical agents is how the drug delivery system (DDS) is designed.
Meanwhile, when nucleic acids are administered to the body as is, they are rapidly degraded and thus fail to work. Accordingly, such nucleic acids are usually administered by using a carrier such as a viral vector, liposome, or atelocollagen as a DDS.
However, nucleic acid pharmaceutical agents have a serious disadvantage in that the carrier itself may induce an adverse immune response or such in the body and thus not only the nucleic acid but also carrier must be assessed for its influence on the body. For example, according to a report, atelocollagen, when used as a carrier, induces a hypersensitive immune reaction to calf dermis derived collagen; the instruction manual (Non-patent Document 1) attached to the product named Koken Atelocollagen implant (syringe type) describes that adverse effects were clinically found in 24 of a total of 1,192 patients.
Another problem is that, even when a carrier is used, normally, the introduced nucleic acid can only be retained for about one week.
Prior art documents include, for example, Patent Documents 1 to 7 listed below. However, all of these inventions use carriers. Thus, the above-described problems still remain unsolved.
[Patent Document 1] Japanese Patent Application Kohyo Publication No. (JP-A) 2003-516365 (unexamined Japanese national phase publication corresponding to a non-Japanese international publication)    [Patent Document 2] JP-A (Kohyo) 2005-538943    [Patent Document 3] JP-A (Kohyo) H09-505575    [Patent Document 4] Japanese Patent Application Saikohyo Publication No. (JP-A) WO01-093856 (unexamined Japanese national phase publication corresponding to a Japanese international publication    [Patent Document 5] JP-A (Kohyo) 2005-503199    [Patent Document 6] Japanese Patent Application Kokai Publication No. (JP-A) 2007-119498 (unexamined, published Japanese patent application)    [Patent Document 7] (Granted/Registered) Japanese Patent No. 4054352    [Non-patent Document 1] Instruction manual attached to the product named Koken Atelocollagen implant (syringe type)